CoChat
Sign Up
Cited by 1,663

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Role of histone H2A ubiquitination in Polycomb silencing

Wang, Hengbin, Wang, Liangjun, Erdjument-Bromage, Hediye, Vidal, Miguel, Tempst, Paul, Jones, Richard S., Zhang, Yi·2004·Nature
DOI 10.1038/nature02985
Open this paper in CoChat — free account

Abstract

Covalent modification of histones is important in regulating chromatin dynamics and transcription. One example of such modification is ubiquitination, which mainly occurs on histones H2A and H2B. Although recent studies have uncovered the enzymes involved in histone H2B ubiquitination and a 'cross-talk' between H2B ubiquitination and histone methylation, the responsible enzymes and the functions of H2A ubiquitination are unknown. Here we report the purification and functional characterization of an E3 ubiquitin ligase complex that is specific for histone H2A. The complex, termed hPRC1L (human Polycomb repressive complex 1-like), is composed of several Polycomb-group proteins including Ring1, Ring2, Bmi1 and HPH2. hPRC1L monoubiquitinates nucleosomal histone H2A at lysine 119. Reducing the expression of Ring2 results in a dramatic decrease in the level of ubiquitinated H2A in HeLa cells. Chromatin immunoprecipitation analysis demonstrated colocalization of dRing with ubiquitinated H2A at the PRE and promoter regions of the Drosophila Ubx gene in wing imaginal discs. Removal of dRing in SL2 tissue culture cells by RNA interference resulted in loss of H2A ubiquitination concomitant with derepression of Ubx. Thus, our studies identify the H2A ubiquitin ligase, and link H2A ubiquitination to Polycomb silencing.

Overview

Integrity signals

Registry

Crossref · 10.1038/nature02985

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Show all 3 references

Research works printed but not linked: 26

  1. Jenuwein, T. & Allis, C. D. Translating the histone code. Science 293, 1074–1080 (2001) · DOI · Paper page
  2. Zhang, Y. & Reinberg, D. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev. 15, 2343–2360 (2001) · DOI
  3. Zhang, Y. Transcriptional regulation by histone ubiquitination and deubiquitination. Genes Dev. 17, 2733–2740 (2003) · DOI
  4. Robzyk, K., Recht, J. & Osley, M. A. Rad6-dependent ubiquitination of histone H2B in yeast. Science 287, 501–504 (2000) · DOI
  5. Hwang, W. W. et al. A conserved RING finger protein required for histone H2B monoubiquitination and cell size control. Mol. Cell 11, 261–266 (2003) · DOI
  6. Wood, A. et al. Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter. Mol. Cell 11, 267–274 (2003) · DOI
  7. Sun, Z. W. & Allis, C. D. Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature 418, 104–108 (2002) · DOI
  8. Dover, J. et al. Methylation of histone H3 by COMPASS requires ubiquitination of histone H2B by Rad6. J. Biol. Chem. 277, 28368–28371 (2002) · DOI
  9. Nickel, B. E. & Davie, J. R. Structure of polyubiquitinated histone H2A. Biochemistry 28, 964–968 (1989) · DOI
  10. Lee, S. J. et al. E3 ligase activity of RING finger proteins that interact with Hip-2, a human ubiquitin-conjugating enzyme. FEBS Lett. 503, 61–64 (2001) · DOI
  11. Satijn, D. P. et al. RING1 is associated with the polycomb group protein complex and acts as a transcriptional repressor. Mol. Cell. Biol. 17, 4105–4113 (1997) · DOI
  12. Fritsch, C., Beuchle, D. & Muller, J. Molecular and genetic analysis of the Polycomb group gene Sex combs extra/Ring in Drosophila. Mech. Dev. 120, 949–954 (2003) · DOI
  13. Gorfinkiel, N. et al. The Drosophila Polycomb group gene Sex combs extra encodes the ortholog of mammalian Ring1 proteins. Mech. Dev. 121, 449–462 (2004) · DOI
  14. Francis, N. J., Saurin, A. J., Shao, Z. & Kingston, R. E. Reconstitution of a functional core polycomb repressive complex. Mol. Cell 8, 545–556 (2001) · DOI
  15. Levine, S. S. et al. The core of the polycomb repressive complex is compositionally and functionally conserved in flies and humans. Mol. Cell. Biol. 22, 6070–6078 (2002) · DOI
  16. Wang, H. et al. mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9 of histone H3 to cause transcriptional repression. Mol. Cell 12, 475–487 (2003) · DOI
  17. Vassilev, A. P., Rasmussen, H. H., Christensen, E. I., Nielsen, S. & Celis, J. E. The levels of ubiquitinated histone H2A are highly upregulated in transformed human cells: partial colocalization of uH2A clusters and PCNA/cyclin foci in a fraction of cells in S-phase. J. Cell Sci. 108, 1205–1215 (1995) · DOI
  18. Cao, R. & Zhang, Y. SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex. Mol. Cell 15, 57–67 (2004) · DOI
  19. Voncken, J. W. et al. Rnf2 (Ring1b) deficiency causes gastrulation arrest and cell cycle inhibition. Proc. Natl Acad. Sci. USA 100, 2468–2473 (2003) · DOI
  20. Wang, L. et al. Hierarchical recruitment of polycomb group silencing complexes. Mol. Cell 14, 637–646 (2004) · DOI
  21. Kao, C. F. et al. Rad6 plays a role in transcriptional activation through ubiquitylation of histone H2B. Genes Dev. 18, 184–195 (2004) · DOI
  22. Ng, H. H., Xu, R. M., Zhang, Y. & Struhl, K. Ubiquitination of histone H2B by Rad6 is required for efficient Dot1-mediated methylation of histone H3 lysine 79. J. Biol. Chem. 277, 34655–34657 (2002) · DOI
  23. Briggs, S. D. et al. Gene silencing: trans-histone regulatory pathway in chromatin. Nature 418, 498 (2002) · DOI
  24. Devroe, E., Erdjument-Bromage, H., Tempst, P. & Silver, P. A. Human Mob proteins regulate the NDR1 and NDR2 serine-threonine kinases. J. Biol. Chem. 279, 24444–24451 (2004) · DOI
  25. Plath, K. et al. Role of histone H3 lysine 27 methylation in X inactivation. Science 300, 131–135 (2003) · DOI
  26. Schoorlemmer, J. et al. Ring1A is a transcriptional repressor that interacts with the Polycomb-M33 protein and is expressed at rhombomere boundaries in the mouse hindbrain. EMBO J. 16, 5930–5942 (1997) · DOI

Cited by

Metadata

Authors
Wang, H., Wang, L., Erdjument-Bromage, H., Vidal, M., Tempst, P., Jones, R. S., & Zhang, Y.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2004-09-22
Volume
431
Issue
7010
Pages
873-878
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/nature02985
Cited by
1,663
References
3
Language
en
Licence
www.springer.com/tdm (tdm)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review